Various eye diseases require treatment by the application of liquid preparations, administered to contact the eye. Eyedrops are also frequently required by wearers of contact lenses. Dry eye disease is a serious condition which requires the repeated application of eye drops per day. Conventional eye drops are based on isotonic solutions of various inorganic salts, with or without "non-ionic" substances (see U.S. Pat. No. 4,409,205), frequently with an added high-molecular weight substance which increases the viscosity of the drops.
Amongst frequently used polymeric substances there may be mentioned methyl cellulose, hydroxy ethyl cellulose, polyvinyl alcohol, polyvinylpyrrolidone, hyaluronic acid, and the like. The viscosity is generally 1 cp to 30 cp.
It is known that at a viscosity of about above 15 cp a discomfort is experienced by most persons, see Adler C. A. et al. The Effect of Viscosity of the Vehicle on the Penetration of Fluorescein into the Human Eye, Exp. Eye Res. 11, 34-42 (1971) and Patton T. F. et al., Occular Evaluation of Polyvinyl Vehicle in Rabbits, J Pharm Sci. 64, 1312-1316, 1975. In view of this most eyedrops have a viscosity in the 2 cp to 5 cp range, even when it is known that a higher viscosity will result in a prolonged action. Therefore, isotonic solutions containing inorganic salts have drawbacks as regards viscosity and physiological characteristics, as solutions containing salts above a certain level do not undergo changes of viscosity upon application of a shear force.
Shively describes in U.S. Pat. No. 4,409,205 Ophthalmic Solutions, which have a salt (sodium chloride) content of from 0.1 weight per cent to about 7.5 weight per cent, in combination with a non-ionic polymer. Extensive experiments have shown that non-ionic polymers do not give solutions having non-Newtonian rheological properties. Furthermore, the salt content which is much above the upper limit stipulated according to the present invention would destroy any such properties, if these would have been present. It is clear that Shively did not intend to prepare non-Newtonian solutions, and he did never obtain such solutions by chance as his ingredients preclude such rheological properties.
Gressel, in WO 94/04681, provides a liquid ophthalmic composition comprising a polyanionic polymer for use as a long-lasting artificial tear. His product, as exemplified and as claimed, relates to a viscous liquid preparation containing 0.05% to 0.5 by weight of a polyanionic polymer in combination with sodium chloride as preferred tonicity agent. He actually exemplifies gels as evident from the viscosity data of all examples. The high sodium chloride content of Gressel will destroy non-Newtonian properties of all the compositions of the present invention.
The preparations of the present invention overcome to a large extent the drawbacks of this kind, since they have a certain viscosity at a low shear rate, which shear rate corresponds to that of an open eye, while when the eye blinks the viscosity of the composition decreases in a pronounced manner to the comfortable range of about 2 cp to about 15 cp, which mimics the behavior of natural tears.
None of patents WO 84/04861--Alcon, U.S. Pat. No. 4,620,979--Schachan or U.S. Pat. No. 4,540,568--Trager describe eye drops which are humectants and the viscosity of which is markedly shear dependent.